This invention relates to a conjugate (M-P-E) formed by binding a magnetic material (M) and a physioloqically active substance (E) to each other through a polyethylene glycol derivative (P) which is an amphiphatic substance for both of water and organic solvents, having physiological activity stably dispersed or dissolved as colloid in both of aqueous solutions and organic solvents, and to a bioreactor enabling application to or rocovery of physiologically active substances the liquid state by utilizing the magnetic properties.
For example, enzymes have been generally dealt with as bioreactors in aquieous solutions, and if their physiological activites can be exerted in organic solvents and utilized for organic syntheses and the like, application range and possibility of biotechnology can be greatly broadened. In short, if enzymes can be catalytic efficiency therein, they can become utilized for more reactions such as reverse reactions of hydrolysis or enzymatic treatment of hydrophobic substances only slightly soluble in water. Furtherwise, other proteins than enzymes can be solubilized in organic solvents and the functions of the proteins can be exhibited in organic solvents. Accordingly, the present inventor has made it possible to solubilize enzymes in orqanic solvents by modification with amphiphatic polymers (Japanese Unexamined Patent Publication No. 156395/1985). However, for utilizing generally physiologically active substances, recovery and reutilization of these are required. As the method for recovery of enzyme proteins, in place of the method in which enzyme proteins are insolubilized by binding with a polymeric or inorganic material carrier and recovered by sedimentation or centrifugation, magnetic separation enabling rapid and simple separation is recently attracting attention. Among these methods, there may be included the method in which proteins are directly adsorbed on the surfaces of magnetic material particles, the method in which the magnetic material particle surfaces are adsorbed or coated with an organic polymer (polyacrylamide, dextran, starch, bovine serum albumin, cellulose) and proteins are then bound thereto, and electromagnets in general can separate magnetic materials with particle sizes to about 30 nm, and superconductive electromagnets can separate those with further smaller sizes. However, these conjugates (M-E) can be dispersed only in aqueous solutions, but agglomerated in organic solvents to form a great mass, which cannot be used. Accordingly, studies have been made intensiely about the technique for dispersing or dissolving as colloid the conjugates (M-E) of magnetic materials and physiologically by active substances such as proteins in aqueous solutions and organic solvents and consequently the present invention has been accomplished.